Apoprotein B (apoB) is produced by the liver as a major structural protein of very low density lipoprotein (VLDL). Interactions of VLDL with lipopytic enzymes in the vascular space are believed to be the sole pathway for the formation of plasma low density lipoprotein (LDL) in man. Our preliminary kinetic studies in the cynomolgus monkey using in vitro radioiodinated lipoproteins suggested that, in addition to a significant contribution of apoB to LDL from plasma VLDL, the monkey requires a second source of apoB. Four hypotheses are postulated to characterize this source: l. ApoB is secreted solely as VLDL. Due to an extremely rapid conversion of a subpopulation of nascent VLDL preferentially to LDL, standard venous sampling failed to provide a true tracer for VLDL metabolism. 2. ApoB is secreted as VLDL but also as IDL. 3. ApoB is secreted both as VLDL and as LDL in this animal system. 4. ApoB is secreted soly as VLDL. Experimental artefacts introduced with the in vitro preparation of the tracer resulted in the finding of these studies. The se hypotheses will be systematically tested in a series of turnover studies using both endogeneous (3H-leucine) and exogeneous (125I and l3lI) tracers. Multicompartmental analysis will be used to analyze the specific activity of apoB in VLDL, IDL and LDL. Direct hepatic vein catherization will be performed to obtain nascent VLDL. Comparison will be made between hepatic VLDL and peripheral plasma VLDL with respect to composition, size distribution, and in vivo kinetics.